Hopkins grows its own bone orchard

Johns Hopkins Hospital is assembling a team of scientists that will work to perfect a kind of biological alchemy that has already succeeded in turning muscle tissue into bone.

Experiments with manipulation of the body's own repair mechanisms suggest human beings may soon be able to generate their own skeletal replacement parts right inside their own bodies.

Hip joints worn down by age or disease, facial bones damaged by accident or congenital deformity, and slow-healing fractures might all be repaired or replaced with the patient's own bone tissue, manufactured to precise specifications inside his own body.

"We see this as the wave of the future," said Dr. Richard N. Stauffer, the newly appointed director of Hopkins' orthopedics department. "We have definitely entered a new era in medicine and research, and without question we have entered a new era of orthopedic medicine." In time, he said, today's sophisticated artificial implants, pins, braces and other mechanical prosthetic devices will begin to seem clumsy and primitive.

The first experiments using human subjects may begin at Hopkins in the next several months, Dr. Stauffer said, although he declined to describe the project. It may be five years before the technology begins to be more generally available.

Hopkins' new 10-member Laboratory for Musculoskeletal Research, which opened officially this month, will be led by A. Hari Reddi, Ph.D., a Hopkins cell biologist formerly with the National Institutes of Health in Bethesda.

In experiments on rats, Dr. Reddi and colleagues at NIH and Washington University School of Medicine in St. Louis, have already transformed flaps of thigh muscle into bones molded in the shape of the rat's femoral head -- the upper thigh bone and hip joint.

That bone is the rat counterpart of the hip joint so often replaced with artificial devices in the elderly.

The research showed that the bone muscle transformed itself into bone because it was stimulated by injection with osteogenin, a recently purified natural protein that the body produces to stimulate bone growth. The shaping was achieved by clamping the muscle -- which remained attached to its blood supply -- into a rubber mold made in the form of the femoral head.

The whole assembly was then implanted inside the rat's abdominal walls for 10 days.

The new bone appears to have a normal internal structure, Dr. Reddi said. Additional tests will determine whether the generated bone is a strong as the original.

Scientists have long known that bone had remarkable powers of regeneration. Through a "cascading" sequence of biological -Z responses, Dr. Reddi said, the bone first creates a cellular "callous" at the injury site, then transforms it into cartilage, and finally regenerated bone tissue.

In this way a broken bone is capable of spontaneously regenerating itself, filling in gaps and knitting itself back together.

"There has been a continuing quest to find what is the principle of this," Dr. Reddi said.

But in the meantime, surgeons are still often faced with bone injuries or defects that go beyond the body's own reconstructive powers, according to Dr. Reddi's report of his work last fall in the Journal of the American Medical Association.

The capacity of certain bone proteins to induce bone growth in other tissues has been known since the 1940s. Early experiments used bone extracts to produce bone growth in rabbit muscle.

Dr. Reddi and his colleagues have spent the last 20 years searching for and purifying that powerful bone growth protein, called osteogenin, and identifying its genetic codes.

They found that it existed in exceedingly minute amounts in the body, constituting barely a billionth of the bone's mass by weight. But they have now cloned the protein and it is being produced in useful quantities in a half dozen forms by recombinant DNA technology at several commercial bioengineering laboratories. Its potential for healing is enormous, Stauffer said.